Predicting Female-Predominant Cardiovascular Dissections via multi-scale Hormonal, Imaging, and Biomechanical Integration

Obiettivo

For decades, cardiovascular biomechanics has treated women as “small men,” assuming biological sex has little impact on vascular function. This bias has obscured key mechanisms driving female-predominant diseases such as Spontaneous Coronary Artery Dissection (SCAD), where existing models fail to explain why and when arteries rupture in women.

DISSEX will overturn this paradigm by developing a sex-aware multiscale framework to predict vascular dissection risk. The project will generate personalized rupture-risk maps to transform diagnosis, prediction, and treatment planning of cardiovascular dissections. To achieve this, DISSEX will address three major challenges: (1) quantify how human coronary arteries respond to systemic hormonal fluctuations and biomechanical stress; (2) determine how hormonal and mechanical factors interact in female-predominant dissections; and (3) reveal the multiscale mechanisms driving coronary dissection.

We hypothesize that integrating systemic drivers – sex hormones, stress, and genetic predisposition – with imaging-derived biomechanical data in an explainable, physics-informed multiscale model will enable local rupture-risk prediction with unprecedented precision. To test this, we will:
Aim 1: quantify gender-specific coronary cellular responses to systemic and biomechanical stimuli via advanced ex vivo analyses;
Aim 2: model cross-scale interactions using Physics-Informed AI;
Aim 3: identify triggering factors in de novo SCAD and in genetically predisposed populations (Turner and Marfan Syndromes).

Ultimately, DISSEX will ambitiously bridge vascular biology, biomechanics, and AI in a fully integrative framework – and through this approach it will redefine the role of gender in cardiovascular biomechanics and open a new path toward precision care of cardiovascular dissections.